Trial Outcomes & Findings for Etrasimod Versus Placebo for the Treatment of Moderately Active Ulcerative Colitis (NCT NCT04607837)

Last Updated: 2025-07-15

Results Overview

MMS is used to assess disease activity in participants with UC and has following components: endoscopic score(ES),rectal bleeding(RB),stool frequency(SF).Each component score ranges from 0 to 3(0=normal,1=mild,2=moderate,3=severe); higher scores indicating more severe disease.ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy,scores ranged from 0(normal or inactive disease) to 3(severe disease \[spontaneous bleeding, ulceration\]).RB reported most severe amount of blood passed per rectum in 24-hour period,scores ranged from 0(no blood seen) to 3(blood alone passes).SF reported number of stools in 24-hour period relative to normal number of stools for that participant in same period,scores ranged from 0(normal number of stools) to 3(5 or more stools than normal).CR per FDA draft guidance defined as:SF=0 or 1 and no greater than baseline, RB=0,ES less than or equal to (\<=)1(excluding friability).Percentage of participants achieving CR at Week 52 was evaluated.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

234 participants

Primary outcome timeframe

Week 52

Results posted on

2025-07-15

Participant Flow

A total of 234 participants with moderately active ulcerative colitis (UC) were enrolled in the study.

Participant milestones

Participant milestones
Measure	Etrasimod Participants with moderately active UC were randomized to receive Etrasimod 2 milligrams (mg) tablet orally once daily (QD) for 52-Week.	Placebo Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Overall Study STARTED	155	79
Overall Study Safety Set	154	79
Overall Study Primary Analysis Set	127	60
Overall Study COMPLETED	97	34
Overall Study NOT COMPLETED	58	45

Reasons for withdrawal

Reasons for withdrawal
Measure	Etrasimod Participants with moderately active UC were randomized to receive Etrasimod 2 milligrams (mg) tablet orally once daily (QD) for 52-Week.	Placebo Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Overall Study Adverse Event	8	2
Overall Study Withdrawal by Subject	8	7
Overall Study Physician Decision	2	0
Overall Study Lack of Efficacy	2	0
Overall Study Participant terminated by sponsor	1	0
Overall Study Disease worsening	36	36
Overall Study Other	1	0

Baseline Characteristics

Etrasimod Versus Placebo for the Treatment of Moderately Active Ulcerative Colitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Etrasimod n=154 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=79 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.	Total n=233 Participants Total of all reporting groups
Age, Continuous	41.6 Years STANDARD_DEVIATION 13.15 • n=5 Participants	40.8 Years STANDARD_DEVIATION 13.00 • n=7 Participants	41.3 Years STANDARD_DEVIATION 13.08 • n=5 Participants
Sex: Female, Male Female	63 Participants n=5 Participants	40 Participants n=7 Participants	103 Participants n=5 Participants
Sex: Female, Male Male	91 Participants n=5 Participants	39 Participants n=7 Participants	130 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	146 Participants n=5 Participants	73 Participants n=7 Participants	219 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	143 Participants n=5 Participants	67 Participants n=7 Participants	210 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 52

Outcome measures

Outcome measures
Measure	Etrasimod n=127 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=60 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Percentage of Participants Achieving Clinical Remission (CR) at Week 52 Using Modified Mayo Score (MMS)	26.0 Percentage of participants	18.3 Percentage of participants

SECONDARY outcome

Timeframe: Week 12

MMS is used to assess disease activity in participants with UC and has following components: ES, RB and SF. Each component score ranges from 0 to 3 (0=normal, 1=mild, 2=moderate, 3=severe); higher scores indicating more severe disease. ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, scores ranged from 0 (normal or inactive disease) to 3 (severe disease \[spontaneous bleeding, ulceration\]). RB reported the most severe amount of blood passed per rectum in a 24-hour period, scores ranged from 0 (no blood seen) to 3 (blood alone passes). SF reported number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, score ranged from 0 (normal number of stools) to 3 (5 or more stools than normal). CR per FDA draft guidance was defined as: SF=0 or =1 and no greater than baseline, RB=0, and ES \<=1 (excluding friability). Percentage of participants achieving CR at Week 12 was evaluated in this endpoint.

Outcome measures

Outcome measures
Measure	Etrasimod n=127 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=60 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Percentage of Participants Achieving Clinical Remission at Week 12 Using MMS	28.3 Percentage of participants	11.7 Percentage of participants

SECONDARY outcome

Timeframe: Week 52

Endoscopic improvement was defined as ES \<=1 (excluding friability). ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0 (normal or inactive disease) to 3 (severe disease \[spontaneous bleeding, ulceration\]), higher scores = more severity. Percentage of participants achieving endoscopic improvement at Week 52 was evaluated in this endpoint.

Outcome measures

Outcome measures
Measure	Etrasimod n=127 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=60 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Percentage of Participants Achieving Endoscopic Improvement at Week 52	32.3 Percentage of participants	23.3 Percentage of participants

SECONDARY outcome

Timeframe: Week 52

Symptomatic remission was defined as SF =0 (or = 1 with a \>= 1 point decrease from baseline) and RB =0. SF subscore: reported number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, scores ranged from 0 (normal number of stools) to 3 (5 or more stools than normal), higher scores = more severity. RB subscore: reported the most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0 (no blood seen) to 3 (blood alone passes), higher scores = more severity. Percentage of participants achieving symptomatic remission at Week 52 was evaluated in this endpoint.

Outcome measures

Outcome measures
Measure	Etrasimod n=127 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=60 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Percentage of Participants Achieving Symptomatic Remission at Week 52	37.0 Percentage of participants	30.0 Percentage of participants

SECONDARY outcome

Timeframe: Week 52

Complete symptomatic remission was defined as participants with RB = 0 and SF = 0. SF subscore: reported number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, scores ranged from 0 (normal number of stools) to 3 (5 or more stools than normal), higher scores = more severity. RB subscore: reported the most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0 (no blood seen) to 3 (blood alone passes), higher scores = more severity. Percentage of participants achieving complete symptomatic remission at Week 52 was evaluated in this endpoint.

Outcome measures

Outcome measures
Measure	Etrasimod n=127 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=60 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Percentage of Participants Achieving Complete Symptomatic Remission at Week 52	20.5 Percentage of participants	20.0 Percentage of participants

SECONDARY outcome

Timeframe: Week 52

Histologic-endoscopic mucosal improvement was defined as ES \<=1 (excluding friability) with Geboes score \<2.0. ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0 (normal or inactive disease) to 3 (severe disease \[spontaneous bleeding, ulceration\]), higher scores = more severity. The Geboes score grading system was a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher Geboes score indicated more severe disease. Percentage of participants achieving mucosal improvement at Week 52 was evaluated in this endpoint.

Outcome measures

Outcome measures
Measure	Etrasimod n=127 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=60 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Percentage of Participants Achieving Histologic-Endoscopic Mucosal Improvement at Week 52	25.2 Percentage of participants	15.0 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 12 and 52 [Combined]

MMS is used to assess disease activity in participants with UC and has following components: ES, RB and SF. Each component score ranges from 0 to 3 (0= normal, 1= mild, 2= moderate, 3= severe); higher scores = more severe disease. ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0 (normal or inactive disease) to 3 (severe disease). RB: reported the most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0 (no blood seen) to 3 (blood alone passes). SF reported number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, score ranged from 0 (normal number of stools) to 3 (5 or more stools than normal). Clinical remission per FDA draft guidance: SF =0 or =1 and no greater than baseline, RB =0, and ES \<=1 (excluding friability). Percentage of participants who achieved clinical remission at both the time points Week 12 and Week 52 \[Combined\] are reported.

Outcome measures

Outcome measures
Measure	Etrasimod n=127 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=60 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Percentage of Participants Achieving Clinical Remission at Both Weeks 12 and 52 [Combined] Using MMS	16.5 Percentage of participants	5.0 Percentage of participants

SECONDARY outcome

Timeframe: Week 52

Population: Primary analysis set included all randomized participants who received at least 1 dose of study treatment with baseline MMS \[total score range: 0 to 9, higher score = more severity\] 4-6, baseline ES greater than or equal to (\>=2) and baseline RB score \>=1. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure who received oral corticosteroids for UC at baseline.

MMS has following components:ES, RB and SF. Each component score ranges from 0 to 3(0=normal,1=mild,2=moderate,3=severe); higher scores indicating more severe disease. ES:worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0(normal or inactive disease)to 3(severe disease). RB:most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0(no blood seen)to 3(blood alone passes). SF:number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, score ranged from 0(normal number of stools)to 3(5 or more stools than normal). CR per FDA draft guidance as: SF =0 or =1 and no greater than baseline, RB=0, and ES \<=1(excluding friability). 12-week corticosteroid-free CR was defined as CR at Week 52 and corticosteroid-free for \>=12 weeks immediately prior to Week 52. The baseline was balanced between treatment groups and representative of participants with mildly to moderately active UC.

Outcome measures

Outcome measures
Measure	Etrasimod n=37 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=18 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Percentage of Participants With 12-Week Corticosteroid-Free Clinical Remission at Week 52 Among Participants Receiving Corticosteroids at Baseline Using MMS	16.2 Percentage of participants	16.7 Percentage of participants

SECONDARY outcome

Timeframe: Week 52

MMS has following components: ES, RB and SF. Each component score ranges from 0 to 3 (0=normal,1=mild,2=moderate,3=severe); higher scores indicating more severe disease. ES: worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0(normal or inactive disease) to 3 (severe disease). RB: most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0(no blood seen) to 3 (blood alone passes). SF: number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, score ranged from 0(normal number of stools) to 3 (5 or more stools than normal). CR per FDA draft guidance as: SF =0 or =1 and no greater than baseline, RB=0, and ES \<=1(excluding friability). 12-week corticosteroid-free CR was defined as CR at Week 52 and corticosteroid-free for \>=12 weeks immediately prior to Week 52.

Outcome measures

Outcome measures
Measure	Etrasimod n=127 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=60 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Percentage of Participants With 12-Week Corticosteroid-Free Clinical Remission at Week 52 Using MMS	25.2 Percentage of participants	16.7 Percentage of participants

SECONDARY outcome

Timeframe: Week 52

MMS has following components: ES, RB and SF; each ranged as 0=normal,1=mild,2=moderate,3=severe; total MMS score 0-9; higher scores=more severe disease. ES:worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0(normal or inactive disease)to 3(severe disease). RB:most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0(no blood seen) to 3(blood alone passes). SF:number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, score ranged from 0(normal number of stools)to 3(5 or more stools than normal). CR per FDA draft guidance as: SF =0 or =1 and no greater than baseline, RB=0, and ES \<=1(excluding friability). 4-week corticosteroid-free CR was defined as CR at Week 52 and corticosteroid-free for \>=4 weeks immediately prior to Week 52. The baseline was balanced between treatment groups and representative of participants with mildly to moderately active UC.

Outcome measures

Outcome measures
Measure	Etrasimod n=20 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=10 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Percentage of Participants Achieving 4-Week Corticosteroid-Free Clinical Remission at Week 52 Among Participants Receiving Corticosteroids at Baseline Using MMS	30.0 Percentage of participants	30.0 Percentage of participants

SECONDARY outcome

Timeframe: Week 52

MMS has following components: ES, RB and SF. Each component score ranges from 0 to 3 (0=normal,1=mild,2=moderate,3=severe); where total score is sum of three components giving total MMS score as 0 to 9; higher scores indicating more severe disease. ES: worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0(normal or inactive disease) to 3 (severe disease). RB: most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0(no blood seen) to 3 (blood alone passes). SF: number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, score ranged from 0 (normal number of stools) to 3 (5 or more stools than normal). CR per FDA draft guidance as: SF =0 or =1 and no greater than baseline, RB=0, and ES \<=1(excluding friability). 4-week corticosteroid-free CR was defined as CR at Week 52 and corticosteroid-free for \>=4 weeks immediately prior to Week 52.

Outcome measures

Outcome measures
Measure	Etrasimod n=127 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=60 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Percentage of Participants With 4-Week Corticosteroid-Free Clinical Remission at Week 52 Using MMS	25.2 Percentage of participants	16.7 Percentage of participants

SECONDARY outcome

Timeframe: Week 12

Population: Primary analysis set included all randomized participants who received at least 1 dose of study treatment with baseline MMS 4-6, baseline ES \>=2 and baseline RB score \>=1.

Clinical response was defined as a \>=2-point and \>=30 percentage (%) decrease from baseline in MMS, and a \>=1-point decrease from baseline in RB subscore or an absolute RB subscore \<=1 and is as per FDA draft guidance. MMS was used to assess disease activity in participants with UC and has following components: ES, RB and SF. Each component score ranges from 0 to 3 (0= normal, 1= mild, 2= moderate, 3= severe); where total score is sum of three components giving total MMS score as 0 to 9; higher scores indicating more severe disease. ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0 (normal or inactive disease) to 3 (severe disease \[spontaneous bleeding, ulceration\]). Percentage of participants achieving clinical response at Week 12 was evaluated in this endpoint.

Outcome measures

Outcome measures
Measure	Etrasimod n=127 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=60 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Percentage of Participants Achieving Clinical Response at Week 12 Using MMS	55.9 Percentage of participants	36.7 Percentage of participants

SECONDARY outcome

Timeframe: Week 52

Population: Primary analysis set included all randomized participants who received at least 1 dose of study treatment with baseline MMS 4-6, baseline ES \>=2 and baseline RB score \>=1.

Clinical response was defined as a \>=2-point and \>=30 % decrease from baseline in MMS, and a \>=1-point decrease from baseline in RB subscore or an absolute RB subscore \<=1 and is as per FDA draft guidance. MMS is used to assess disease activity in participants with UC and has following components: ES, RB and SF. Each component scores ranges from 0 to 3 (0= normal, 1= mild, 2= moderate, 3= severe); where total score is sum of three components giving total MMS score as 0 to 9; higher scores indicating more severe disease. ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, scores ranged from 0 (normal or inactive disease) to 3 (severe disease \[spontaneous bleeding, ulceration\]). Percentage of participants achieving clinical response at Week 52 was evaluated in this endpoint.

Outcome measures

Outcome measures
Measure	Etrasimod n=127 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=60 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Percentage of Participants Achieving Clinical Response at Week 52 Using MMS	44.1 Percentage of participants	38.3 Percentage of participants

SECONDARY outcome

Timeframe: Week 12

Endoscopic improvement was defined as ES \<=1 (excluding friability). ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, scores ranged from 0 (normal or inactive disease) to 3 (severe disease \[spontaneous bleeding, ulceration\]), higher scores = more severity. Percentage of participants achieving endoscopic improvement at Week 12 was evaluated in this endpoint.

Outcome measures

Outcome measures
Measure	Etrasimod n=127 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=60 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Percentage of Participants Achieving Endoscopic Improvement at Week 12	44.1 Percentage of participants	20.0 Percentage of participants

SECONDARY outcome

Timeframe: Week 12

Histologic-endoscopic mucosal improvement was defined as ES \<=1 (excluding friability) with Geboes score \<2.0. ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, scores ranged from 0 (normal or inactive disease) to 3 (severe disease \[spontaneous bleeding, ulceration\]), higher scores = more severity. The Geboes score grading system was a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher Geboes score indicated more severe disease. Percentage of participants achieving mucosal improvement at Week 12 was evaluated in this endpoint.

Outcome measures

Outcome measures
Measure	Etrasimod n=127 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=60 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Percentage of Participants Achieving Histologic-Endoscopic Mucosal Improvement at Week 12	29.1 Percentage of participants	13.3 Percentage of participants

SECONDARY outcome

Timeframe: Week 12

Symptomatic remission was defined as SF =0 (or = 1 with a \>= 1 point decrease from baseline) and RB =0. SF subscore: reported number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, scores ranged from 0 (normal number of stools) to 3 (5 or more stools than normal), higher scores = more severity. RB subscore: reported the most severe amount of blood passed per rectum in a 24-hour period, scores ranged from 0 (no blood seen) to 3 (blood alone passes), higher scores = more severity. Percentage of participants achieving symptomatic remission at Week 12 was evaluated in this endpoint.

Outcome measures

Outcome measures
Measure	Etrasimod n=127 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=60 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Percentage of Participants Achieving Symptomatic Remission at Week 12	36.2 Percentage of participants	25.0 Percentage of participants

SECONDARY outcome

Timeframe: Week 12

Complete symptomatic remission was defined as participants with RB = 0 and SF = 0. SF subscore: reported number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, scores ranged from 0 (normal number of stools) to 3 (5 or more stools than normal), higher scores = more severity. RB subscore: reported the most severe amount of blood passed per rectum in a 24-hour period, scores ranged from 0 (no blood seen) to 3 (blood alone passes), higher scores = more severity. Percentage of participants achieving complete symptomatic remission at Week 12 was evaluated in this endpoint.

Outcome measures

Outcome measures
Measure	Etrasimod n=127 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=60 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Percentage of Participants Achieving Complete Symptomatic Remission at Week 12	20.5 Percentage of participants	20.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 12

ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, scores ranged from 0 (normal or inactive disease) to 3 (severe disease \[spontaneous bleeding, ulceration\]), higher scores = more severity. RB: reported the most severe amount of blood passed per rectum in a 24-hour period, scores ranged from 0 (no blood seen) to 3 (blood alone passes), higher scores = more severity. SF reported number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, score ranged from 0 (normal number of stools) to 3 (5 or more stools than normal), higher scores = more severity. Percentage of participants with reduction from baseline in both ES and RB or in both ES and SF at Week 12 was evaluated in this endpoint. The baseline primary analysis set was balanced between treatment groups and representative of participants with mildly to moderately active UC.

Outcome measures

Outcome measures
Measure	Etrasimod n=127 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=60 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Percentage of Participants Achieving Change From Baseline in Both ES and RB or in Both ES and SF at Week 12	44.9 Percentage of participants	21.7 Percentage of participants

SECONDARY outcome

Timeframe: Week 12

Histologic response based on the Geboes grading system was defined as Geboes score \<=3.1. The Geboes score grading system is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher Geboes score indicated more severe disease. Percentage of participants achieving histologic response based on the Geboes grading system at week 12 was evaluated in this endpoint.

Outcome measures

Outcome measures
Measure	Etrasimod n=127 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=60 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Percentage of Participants Achieving Histologic Response Based on the Geboes Grading System at Week 12	44.9 Percentage of participants	33.3 Percentage of participants

SECONDARY outcome

Timeframe: Week 12

RHI is an evaluative index, derived from the Geboes score, that is designed to be reproducible and responsive to clinically meaningful change in disease activity over time. Histologic response based on RHI was defined as decrease in RHI of \>=7 points from baseline. Total RHI score ranges from 0 (no disease activity) to 33 (severe disease activity), higher score = more severity. Percentage of participants achieving histologic response based on RHI at Week 12 was evaluated in this endpoint.

Outcome measures

Outcome measures
Measure	Etrasimod n=127 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=60 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Percentage of Participants Achieving Histologic Response Based on Robarts Histopathology Index (RHI) at Week 12	46.5 Percentage of participants	35.0 Percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks)

Population: Safety set included all randomized participants who received at least 1 dose of study treatment.

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/ incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and all non-SAEs.

Outcome measures

Outcome measures
Measure	Etrasimod n=154 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=79 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Number of Participants With Adverse Events (AEs)	101 Participants	49 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks)

Population: Safety set included all randomized participants who received at least 1 dose of study treatment.

An AE was any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An AE was therefore any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Severity was classified using common terminology criteria for adverse events (CTCAE), version 5.0, where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = death related to AE. Only those categories in which at least 1 participant had data for any reporting group were reported.

Outcome measures

Outcome measures
Measure	Etrasimod n=154 Participants Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=79 Participants Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Number of Participants With AEs Based on Severity Grade 1	48 Participants	23 Participants
Number of Participants With AEs Based on Severity Grade 2	42 Participants	24 Participants
Number of Participants With AEs Based on Severity Grade 3	11 Participants	2 Participants

Adverse Events

Etrasimod

Serious events: 10 serious events

Other events: 100 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Etrasimod n=154 participants at risk Participants with moderately active UC were randomized to receive Etrasimod 2 mg tablet orally QD for 52-Week.	Placebo n=79 participants at risk Participants with moderately active UC were randomized to receive placebo matched to Etrasimod tablet orally QD for 52-Week.
Gastrointestinal disorders Colitis ulcerative	2.6% 4/154 • Number of events 4 • From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks) Same event may occur as both non-SAE and SAE but are distinct events. An event may be categorised as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE. Safety set included all randomised participants who received at least 1 dose of study treatment.	0.00% 0/79 • From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks) Same event may occur as both non-SAE and SAE but are distinct events. An event may be categorised as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE. Safety set included all randomised participants who received at least 1 dose of study treatment.
General disorders Chest pain	0.65% 1/154 • Number of events 1 • From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks) Same event may occur as both non-SAE and SAE but are distinct events. An event may be categorised as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE. Safety set included all randomised participants who received at least 1 dose of study treatment.	0.00% 0/79 • From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks) Same event may occur as both non-SAE and SAE but are distinct events. An event may be categorised as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE. Safety set included all randomised participants who received at least 1 dose of study treatment.
Hepatobiliary disorders Cholelithiasis	0.65% 1/154 • Number of events 1 • From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks) Same event may occur as both non-SAE and SAE but are distinct events. An event may be categorised as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE. Safety set included all randomised participants who received at least 1 dose of study treatment.	0.00% 0/79 • From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks) Same event may occur as both non-SAE and SAE but are distinct events. An event may be categorised as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE. Safety set included all randomised participants who received at least 1 dose of study treatment.
Infections and infestations Post procedural infection	0.65% 1/154 • Number of events 1 • From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks) Same event may occur as both non-SAE and SAE but are distinct events. An event may be categorised as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE. Safety set included all randomised participants who received at least 1 dose of study treatment.	0.00% 0/79 • From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks) Same event may occur as both non-SAE and SAE but are distinct events. An event may be categorised as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE. Safety set included all randomised participants who received at least 1 dose of study treatment.
Infections and infestations Viral infection	0.65% 1/154 • Number of events 1 • From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks) Same event may occur as both non-SAE and SAE but are distinct events. An event may be categorised as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE. Safety set included all randomised participants who received at least 1 dose of study treatment.	0.00% 0/79 • From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks) Same event may occur as both non-SAE and SAE but are distinct events. An event may be categorised as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE. Safety set included all randomised participants who received at least 1 dose of study treatment.
Injury, poisoning and procedural complications Incisional hernia	0.65% 1/154 • Number of events 1 • From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks) Same event may occur as both non-SAE and SAE but are distinct events. An event may be categorised as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE. Safety set included all randomised participants who received at least 1 dose of study treatment.	0.00% 0/79 • From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks) Same event may occur as both non-SAE and SAE but are distinct events. An event may be categorised as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE. Safety set included all randomised participants who received at least 1 dose of study treatment.
Injury, poisoning and procedural complications Radius fracture	0.65% 1/154 • Number of events 1 • From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks) Same event may occur as both non-SAE and SAE but are distinct events. An event may be categorised as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE. Safety set included all randomised participants who received at least 1 dose of study treatment.	0.00% 0/79 • From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks) Same event may occur as both non-SAE and SAE but are distinct events. An event may be categorised as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE. Safety set included all randomised participants who received at least 1 dose of study treatment.
Injury, poisoning and procedural complications Ulna fracture	0.65% 1/154 • Number of events 1 • From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks) Same event may occur as both non-SAE and SAE but are distinct events. An event may be categorised as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE. Safety set included all randomised participants who received at least 1 dose of study treatment.	0.00% 0/79 • From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks) Same event may occur as both non-SAE and SAE but are distinct events. An event may be categorised as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE. Safety set included all randomised participants who received at least 1 dose of study treatment.
Nervous system disorders Epilepsy	0.65% 1/154 • Number of events 1 • From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks) Same event may occur as both non-SAE and SAE but are distinct events. An event may be categorised as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE. Safety set included all randomised participants who received at least 1 dose of study treatment.	0.00% 0/79 • From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks) Same event may occur as both non-SAE and SAE but are distinct events. An event may be categorised as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE. Safety set included all randomised participants who received at least 1 dose of study treatment.
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/154 • From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks) Same event may occur as both non-SAE and SAE but are distinct events. An event may be categorised as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE. Safety set included all randomised participants who received at least 1 dose of study treatment.	1.3% 1/79 • Number of events 1 • From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks) Same event may occur as both non-SAE and SAE but are distinct events. An event may be categorised as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE. Safety set included all randomised participants who received at least 1 dose of study treatment.

Other adverse events

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